Structural identification for in vivo metabolites of proanthocyanidin B_2.
10.19540/j.cnki.cjcmm.20250331.201
- Author:
Wen-Hui ZHAO
1
;
Hui-Ting TANG
1
;
Jun LI
2
;
Yue-Lin SONG
2
;
Ke ZHANG
2
;
Yun-Fang ZHAO
2
Author Information
1. Research Institute of Chinese Medicine, Beijing University of Chinese Medicine Beijing 102488, China School of Chinese Materia Medica, Beijing University of Chinese Medicine Beijing 102488, China.
2. Research Institute of Chinese Medicine, Beijing University of Chinese Medicine Beijing 102488, China.
- Publication Type:Journal Article
- Keywords:
isomer;
metabolites;
online ER-MS;
proanthocyanidin B_2;
structural identification
- MeSH:
Animals;
Proanthocyanidins/urine*;
Rats;
Male;
Drugs, Chinese Herbal/chemistry*;
Rats, Sprague-Dawley;
Tandem Mass Spectrometry;
Chromatography, High Pressure Liquid;
Feces/chemistry*;
Molecular Structure
- From:
China Journal of Chinese Materia Medica
2025;50(10):2841-2852
- CountryChina
- Language:Chinese
-
Abstract:
Proanthocyanidin B_2(PAC-B_2), a polyphenolic dimeric compound comprising two epicatechin molecules linked by a C-C bond, is extensively found in traditional Chinese medicines, with anti-tumor and anti-oxidant activities. Given the limited bioavailability, a thorough investigation and comprehensive understanding of PAC-B_2 metabolism in vivo are essential for elucidating therapeutic forms and mechanisms. In the present study, ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) in the negative ion mode was employed to acquire the MS/MS information of PAC-B_2 and metabolites in urine and feces samples of the rats administrated with PAC-B_2. Online energy-resolved MS(ER-MS) was applied as supplementary to obtain the full collision energy ramp-MS~2 spectra(FCER-MS~2) of isomers-of-interest, which implied comprehensive MS~2 information of targeted compounds. Finally, the possible metabolic pathways of PAC-B_2 in rats were proposed. The primary fragmentation behaviors of PAC-B_2 in the negative ion mode included quinone methide fission between C_4-C_8 bond, retro Diels-Alder cracking of F-ring, heterocyclic ring fission of C-ring, and neutral loss of small molecules such as H_2O. A total of 25 metabolites were tentatively elucidated in urine and feces samples of rats administrated with PAC-B_2 by fragmentation pattern and reported literature. Two groups of isomers, M3/M4/M5 and M9/M11, were confirmatively differentiated based on the relationships between optimal collision energy provided by FCER-MS~2 and bond properties, including bond length and bond dissociation energy. In addition to the ring-opening and methylation, PAC-B_2 could also be metabolized into epicatechin and low molecular weight phenolic acids, which were subsequently subjected to dehydroxylation, ring-opening, methylation, sulfation, and glucuronidation. The structural information provided by online ER-MS and FCER-MS~2 enabled the differentiation of isomers and improved the identification confidence. More importantly, the present study deeply analyzes the in vivo metabolic pathways of PAC-B_2, providing a basis for the research on the pharmacological mechanism of this compound.
